Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious, debilitating disorder with a wide spectrum of symptoms, including pain, depression, and neurocognitive deterioration. Over 17 million people around the world have ME/CFS, predominantly women with peak onset at 30-50 years. Given the wide spectrum of symptoms and unclear etiology, specific biomarkers for diagnosis and stratification of ME/CFS are lacking. Here we show that actin network proteins in circulating extracellular vesicles (EVs) offer specific non-invasive biomarkers for ME/CFS. We found that circulating EVs were significantly increased in ME/CFS patients correlating to C-reactive protein, as well as biological antioxidant potential. Area under the receiver operating characteristic curve for circulating EVs was 0.80, allowing correct diagnosis in 90-94% of ME/CFS cases. From two independent proteomic analyses using circulating EVs from ME/CFS, healthy controls, idiopathic chronic fatigue, and depression, proteins identified from ME/CFS patients are involved in focal adhesion, actin skeletal regulation, PI3K-Akt signaling pathway, and Epstein-Barr virus infection. In particular, talin-1, filamin-A, and 14-3-3 family proteins were the most abundant proteins, representing highly specific ME/CFS biomarkers. Our results identified circulating EV number and EV-specific proteins as novel biomarkers for diagnosing ME/CFS, providing important information on the pathogenic mechanisms of ME/CFS.
Keywords: Actin network proteins; Circulating EV; ME/CFS; Non-invasive biomarkers.
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Circulating extracellular vesicles as potential biomarkers in chronic fatigue syndrome/myalgic encephalomyelitis: an exploratory pilot study.J Extracell Vesicles. 2018 Mar 22;7(1):1453730. doi: 10.1080/20013078.2018.1453730. eCollection 2018. J Extracell Vesicles. 2018. PMID: 29696075 Free PMC article.
Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome.J Transl Med. 2019 Dec 4;17(1):409. doi: 10.1186/s12967-019-02153-6. J Transl Med. 2019. PMID: 31801546 Free PMC article.
Epstein-Barr Virus dUTPase Induces Neuroinflammatory Mediators: Implications for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.Clin Ther. 2019 May;41(5):848-863. doi: 10.1016/j.clinthera.2019.04.009. Epub 2019 Apr 28. Clin Ther. 2019. PMID: 31040055 Free PMC article.
Neuroinflammation and Cytokines in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Critical Review of Research Methods.Front Neurol. 2019 Jan 10;9:1033. doi: 10.3389/fneur.2018.01033. eCollection 2018. Front Neurol. 2019. PMID: 30687207 Free PMC article. Review.
Inflammatory and oxidative and nitrosative stress cascades as new drug targets in myalgic encephalomyelitis and chronic fatigue syndrome.Mod Trends Pharmacopsychiatry. 2013;28:162-74. doi: 10.1159/000343982. Epub 2013 Feb 27. Mod Trends Pharmacopsychiatry. 2013. PMID: 25224898 Review.